Metastasized Castration Resistant Prostate Cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ
Conditions
Interventions
Trade Name: Jevtana (cabazitaxel)
Product Name: Cabazitaxel/ Jevtana
Product Code: XRP6258
Pharmaceutical Form: Concentrate and solvent for concentrate
Sponsors
Netherlands Cancer Institute
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Histological diagnosis of prostate adenocarcinoma. 2. Able and willing to provide informed consent and to comply with the study procedures 3. Age =18 4. Evidence of bone, visceral and/or lymph node metastases on bone scan, CT-scan or MRI. 5. Must have received at least one prior regimen of docetaxel treatment for at least 12 weeks (four courses) and no other prostate cancer treatments between docetaxel and randomization, other than prednisone. 6. Continued androgen deprivation therapy either by LHRH agonist/ antagonist or orchiectomy. 7. Treatment with curative intent is not an option and patient has an indication for systemic treatment as judged by the medical care provider 8. Evidence of progressive metastatic disease by PSA progression (Prostate Cancer Working Group 3 (PCWG3) criteria: at least 2 rises at a minimum of 1-week intervals. The first PSA value must be = 2 ng/ml) and/or radiological progression as evaluated by chest, abdominal, or pelvic CT/MRI scan and/or bone scan within 28 days of registration (see Appendix III) 9. Poor prognosis disease as defined by any of the following: a) The presence of liver metastases AND/OR b) Development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease AND/OR c) Progressive disease during docetaxel treatment or =65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. Histologic evidence of small cell/neuroendocrine prostate cancer 2. Any treatment other than prednisone between docetaxel and cabazitaxel/abiraterone OR enzalutamide sequence 3. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus). 4. History of severe hypersensitivity reaction (= grade 3) to docetaxel, abiraterone or enzalutamide (whichever applies). 5. History of severe hypersensitivity reaction (= grade 3) to polysorbate 80 containing drugs. 6. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments). 7. Patients who have a concurrent yellow fever vaccination (several weeks before start of treatment) must be excluded. 8. Dementia, altered mental status, or any psychiatric condition, if this is in conflict with the study. 9. Unable to swallow a whole tablet or capsule 10. Contraindications to the use of corticosteroid treatment 11. Symptomatic peripheral neuropathy Grade =2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v.4.0). 12. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and needing no subsequent therapy. 13. Inadequate organ and bone marrow function as evidenced by: a. Hemoglobin 1.5 x ULN Total bilirubin >1 x ULN (except for patients with documented Gilbert’s disease).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): To establish the Clinical Benefit Rate (CBR) in both study arms: Percentage of patients that fulfill the criteria of clinical benefit. Patients are considered to have had a clinical benefit if they have a radiological response of any duration or stable disease for ? 12 weeks, in the absence of symptomatic progression, or objective disease progression. Radiological Response Subjects that have measurable disease at screening will be evaluated for response on the basis of RECIST criteria v1.1, Tumor measurements using physical examination, chest, abdomen, pelvic CT scan, and/or MRI or other appropriate techniques deemed suitable by the investigator will be performed at screening within 28 days of subject registration and repeated at week 6, 12, 18 and 24 followed by every 12 weeks. Symptomatic or objective disease Progression Disease Progression is defined as the development of symptomatic or radiological progression at any time. Progression will be classified as any of the following: 1. Symptomatic progression: worsening of cancer-related symptoms mandating a change in anti-cancer therapy (radiation, chemotherapy or antihormonal therapy) or = 2 level decrease in WHO PS. 2. Radiological progression: RECIST criteria v1.1 for measurable disease and/or appearance of 2 or more 2 new bone lesions on whole body bone scan confirmed on a subsequent scan31. ; Main Objective: • To assess the Clinical Benefit Rate (CBR) in patients with mCRPC and poor prognostic factors treated with cabazitaxel (Arm A) or novel hormonal agents (abiraterone OR enzalutamide) as second-line therapy (Arm B) who have been treated with docetaxel. ; Secondary Objective: • compare the Clinical Benefit Rate (CBR) in both study arms A and B. • determine duration of treatment (DOT), Time To Symptomat | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Formal comparison of the CBR in both study arms. 2. Duration of treatment (DOT); time from randomization to last day of treatment. 3. Time To Symptomatic Progression TTSP; time from randomization to day of worsening of cancer-related symptoms mandating a change in anti-cancer therapy (radiation, chemotherapy or antihormonal therapy) or = 2 level decrease in WHO PS. 4. Time To Radiological Progression (TTRP); time from randomization to day of radiological progression: RECIST criteria v1.1 for measurable disease or appearance of ? 2 new bone lesions on whole body bone scan confirmed on a subsequent scan. 5. Time To PSA Progression (TTPP); time from randomization to PSA progression (PCWG3 criteria: at least 2 rises at a minimum of 1-week intervals. The first PSA value must be = 2 ng/ml). 6. Progression Free Survival (PFS) is defined as the time of start of treatment and the first date of progression on second line treatment as measured by PSA progression, tumor progression, pain progression during treatment, or death. Assessed in patients who are treated with either arms as second line treatment and in patients who crossed over to the other treatment arm. 7. Overall Survival; time from randomization to date of death. Follow up will be maximum 3 years. 8. To evaluate safety and toxicity profile of cabazitaxel and novel hormone agents (abiraterone OR enzalutamide) all Adverse Events (AEs; assessed by CTCAE 4.03 grading) and Serious Adverse Events (SAEs) will be recorded during second line cabazitaxel/abiraterone OR enzalutamide treatment. 9. Quality of Life (QoL) as assessed by FACT-P questionnaire and Pain response as assessed by BPI-S questionnaire and opiate use will be recorded during second line cabazitaxel/abiraterone OR enzalutamide treatment ;Timepoint(s) of evaluation of this end point: A | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Netherlands Cancer Institute
Outcome results
None listed